Passive cutaneous anaphylaxis tests

The synthetic P-o-glucopyranoside 30 was converted to the cyanoglucoside rho-diocyanoside A (38a), which was isolated from the underground part of Rhodiola quadrifida (Pall.) Fisch. et Mey. (Crassulaceae) and found to show antiallergic activity in a passive cutaneous anaphylaxis test in rat. Acetylation of 30 gave an acetate (98% yield) which was subjected to ozonolysis to afford the aldehyde 39. The Horner-Emmons reaction of 39 using diethyl (l-cyanoethyl)phosphonate furnished (Z)-40a (32% yield from 30) and ( )-40b (10% yield from 30). The physical... 

Typical protocols for dermal sensitization, active systemic anaphylaxis, and passive cutaneous anaphylaxis tests are given in the article Animals in Drug Development, in this encyclopedia. In a typical gel-diffusion test, solutions of test compound, egg albumin (positive control), or vehicle (usually saline) are mixed with complete Freund s adjuvant. These mixtures are injected into animals (usually guinea pigs) of the... 

There are other compounds in the literature which seem to have a potentially useful blend of bronchodilator and antiallergy action. Compound IX, having a cromolyn-type structure, is effective in the passive cutaneous anaphylaxis test in rats as well as in the histamine aerosol test in guinea pigs (22). It has less cardiovascular effects than theophylline but causes some CNS stimulation. Compound X is a recent compound which in animals appears to be more potent than theophylline in its bronchodilator/antiallergic actions and also appears to have greater broncho-selectivity (23, 24). 

In all these studies, either serum antibody or the plaque-forming response was tested with the exception of IgE, which was tested by a passive cutaneous anaphylaxis test. In none of the experiments was an attempt made to delineate the cell types that may be stimulated by the retinoid. Therefore, we do not know presently whether the drug acts on B cells, T cells, antigen-presenting cells or other cell types. Three different retinoids were employed and it is not known whether any one in particular may be superior to the others for immunostimula-tion because no comparative studies have been done. 

Chloro-oxazolo[4,5-/i]quinoline-2-carboxylic acid methyl ester was the most active compound in tests for inhibitors of antigen-induced release of histamine in vitro from rat peritoneal mast cells (IC50 of 0.3 p,M) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (ED50 (intraperitoneal) of 0.1 mg/kg in dose 0.5 mg/kg as an inhibitor of the test)—10 times and 60 times more potent, respectively, than the disodium salt of cromoglycic acid (85JMC1255). 

Reaction of 2-aminoquinoline derivatives with BrCH2C0C02Et gave imidazoquinoline-2-carboxylate 473 which upon hydrolysis with sodium hydroxide gave the corresponding acid which had been tested against the passive cutaneous anaphylaxis (78GEP2802493, 78BEP858605) (Scheme 79). 

Passive cutaneous anaphylaxis (PCA)-Test for potential antigenicity of compounds Other... 

Hexahydropyrimido[l,2-a]azepin-4-ones 456, 463, and 467 display analgetic activity (77MI1). 10-Aminomethylene and 10-phenylhydrazino derivatives 478 (R = H) possess weak antiallergic effects in the passive cutaneous anaphylaxis (PCA) test (84JMC1253). 

Comments on the Studies in Rats. Passive cutaneous anaphylaxis in rats has been used extensively in the study of cromo-glycate-like compounds. Upon intravenous administration these compounds can abolish the vascular permeability changes, which follow mediator release from sensitized mast cells. This activity appears at doses which do not inhibit the effects of exogenous mediators. The oral activity of this type of compounds is generally nil and this holds also for doxanthrazole, which was inactive in the standard conditions of our test. 

Passive Cutaneous Anaphylaxis (PCA)—Test for potential antigenicity of compounds... 

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